| Project/Area Number |
26860720
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Hematology
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| Research Institution | Fukushima Medical University |
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Principal Investigator |
UEDA KOKI 福島県立医科大学, 医学部, 助教 (80632190)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 骨髄増殖性腫瘍 / HMGA2 / 骨髄増殖性疾患 |
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| Outline of Final Research Achievements |
To clarify if HMGA2 affect JAK2V617F+ hematopoiesis, we crossed HMGA2-overexpressing mice (ΔHmga2) with JAK2V617F Tg mice (JAK2VF) and obtained ΔHmga2-JAK2VF mice (double-Tg). At 3 months old, leukocytosis, thrombocytosis, anemia and splenomegaly were most severe in double-Tg compared with ΔHmga2 or JAK2VF. ΔHmga2 and JAK2VF survived for over a year, but all double-Tg died within 5 months. Lineage-Sca1+Kit+ cells were most frequent in double-Tg followed by ΔHmga2, indicating HMGA2 contributes to expansion of JAK2V617F+ hematopoietic stem cells (HSC). In competitive/serial transplants, ΔHmga2 and double-Tg cells steadily expanded, while JAK2VF cells were decreased and eventually rejected in 3rd transplant. Thus, HMGA2 may accelerate proliferative hematopoiesis harboring JAK2V617F with expanding MPN HSC. In fact, endogenous HMGA2 is upregulated in JAK2VF with conditional EZH2 KO (EZH2-/-JAK2VF).
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